P2: Neural Substrates of Decision-Making The prevalent use of methamphetamine (METH) among individuals with HIV infection.represents a double epidemic that has serious consequences involving neural and behavioral alterations. Both HIV and METH independently alter brain function within dopaminergic regions, and their comorbidity likely preferentially impacts goal-directed behavior and risky decision-making due to altered reward and punishment processing and expectancy. This is supported by our prior work demonstrating an HIV by METH interaction for fMRI BOLD response to reward expectancy within the ventromedial prefrontal cortex and anterior cingulate, as well as impaired responses within anterior cingulate and striatum during risky decision-making. An emerging concern is the possibility that aging might exacerbate neurocognitive dysfunction already prevalent in HIV infected individuals, particularly on reward-related decision-making and learning behaviors. Building from our prior findings, the aims of the current project involve state-of-the-art multimodal MRI methods that will be used to query both functional brain responses (BOLD/FMRI) and the underlying connectivity between brain regions relevant to the decision-making process (diffusion MRI and resting BOLD). We also aim to determine the modulatory^effects of aging on HIV and/or METH effects. We propose to study four groups of 30 well-characterized individuals stratified by HIV serostatus and METH dependence diagnosis from the primary TMARC cohort (total N=120). Participants will undergo functional magnetic resonance imaging (fMRI) to probe limbic and cognitive circuitry using three experimental paradigms: 1) probabilistic associative learning with positive and negative feedback; 2) risky decision-making; and 3) resting state (task-free) fMRI. Participants will also undergo diffusion MRI to assess white matter integrity within frontostriatal tracts and to examine the relationship between frontostriatal structural and functional connectivity. We will map our neuroimaging and neurobehavioral task data onto the decision-making data gathered in Project 1. Findings will inform a future NIH application investigating re.al-world consequences (e.g., adherence to treatment and risky behavior) of increased reward sensitivity due to HIV/METH and aging.